Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates

Abstract

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

Keywords: Metapneumovirus; Nonhuman primates; Replicon particles; Respiratory syncytial virus; Vaccine.

Figure 1

Detection of hRSV in BAL (A) or nostril (B) following challenge. The level of viable RSV was measured in each compartment by direct plaque assay of samples on HEp-2 cell monolayer cultures. Plaques were visualized by immunoperoxidase staining.

Figure 2

Detection of RSV genome in BAL (A) or nostril (B) following challenge. Primers and probe targeting the hRSV matrix (M) gene were used to detect hRSV genome. Samples with a cycle threshold value less than 40 were considered positive.

Figure 3

Detection of hMPV genome in BAL (A) or nostril (B) following challenge. Primers and probe targeting the hMPV N gene were used to detect hMPV genome. Samples with a cycle threshold value less than 40 were considered positive.